Betaines



United States Patent 3,366,671 BETAINES Frank M. Cowen, North Plainfield, N.J., and Gloria Bellis, New Rochelle, N.Y., assignors to American Cyanamid Company, Stamford, Conn., a corporation of Maine No Drawing. Original application Dec. 28, 1959, Ser. No. 862,087, now Patent No. 3,225,074, dated Dec. 21, 1965. Divided and this application Sept. 1, 1964, Ser. No.

2 Claims. (Cl. 260-50112) This application is a division of application Ser. No. 862,087, filed Dec. 28, 1959, now Patent No. 3,225,074 which in turn is a continuation-in-part of application Ser. No. 547,845, filed Nov. 18, 1955, now abandoned.

The present invention relates to new compositions of matter consisting of betaine derivatives, to the processes of preparing them and to their use as germicides.

It has been found that betaine derivatives may be prepared having the following structural formula:

or R COOMe, wherein x is a whole number from 2 to 4, y is a number from 1 to about 100, R is methyl, ethyl, tolyl or phenyl, and 'Me is hydrogen, ammonium or a metal, particularly an alkali metal or an alkaline earth metal; and R is an alkylene radical C H containing from 1 to 12 carbon atoms and preferably 1-6 carbon atoms. I

Typical specific illustrative examples of R are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tertbutyl, isobutyl, amyl, tert-amyl, isoamyl, hexyl, heptyl, octyl, nonyl, decyl, hendecyl, dodecyl, tridecyl, hexadecyl, octadecyl, eicosyl, etc.; allyl, butenyl, pentenyl, hexenyl, oleyl, linoleyl, linolenyl, etc.; phenyl, phenethyl, tolyl, xylyl, methyl xylyl, benzyl, naphthyl, naphthyl methyl, etc.; cyclohexyl, cyclopentyl, etc.

The bivalent radical M, represented by the partial formulas -C(=A)D, -B-C(=A) and includes, for example, such groupings as aminocarbonyl NH-C(=O), carbonylamino C(=O)NH, carbonyloxy C(=O)O; aminocarbonylamino -NHC(=O)NH; the corresponding thio-groupings; and the substituted imino derivatives wherein the hydrogen of the imino radical is substituted by alkyl, cycloalkyl, alkenyl, aryl, aralkyl and alkaryl groups.

Representative examples of radicals R and R are methylene, ethylene, propylene, butylene, pentamethylene, etc., with the range of carbon atoms being from 1 to 24 and from 1 to 12, respectively.

The hydroxyalkyl radical may be illustrated by such examples as hydroxymethyl, hydroxyethyl, hydroxypropyl, etc. Similarly, the -(C H R H radical may be illustrated by such examples as ethenoxy, diethenoxy, dipropenoxy, triethenoxy, tetraethenoxy, pentaethenoxy,

octaethenoxy, octadecaethenoxy, phenylethenoxy, etc. In the herinafter described illustrative examples, it is to be noted that ethylene oxide is the most commonly used oxide but such has been the case primarily for illustrative purposes and is not to be construed as limitative of the invention. Consequently, other alkylene oxides such as propylene oxide and isobutylene oxide, as well as styrene oxide may be used.

The radical Me may be hydrogen, ammonium or a metal such as sodium, potassium, magnesium, calcium, etc.

The betaines of the present invention are prepared by initially making intermediate products suitable for conversion to the desired betaines. These intermediate products include, for example, (1) tertiary amines containing amide groupings resulting from the reaction of an acid (including thionic acids) and an aminoalkyl-substituted tertiary amine; (2) tertiary amines containing amide groupings resulting from the reaction of an acid (including thionic acids) and an aminoalkyl-substituted secondary amine, followed by further treatment of the reaction product with an alkylene oxide; (3) tertiary amines containing ester groupings resulting from the reaction of an acid and an alkanolamine containing a tertiary amine grouping; (4) tertiary amines containing amide groupings resulting from the condensation of urea and N-substituted ureas with a diamine containing one tertiary amine grouping, etc.

These tertiary amine-intermediate products are then reacted with an omega-halogen-substituted aliphatic acid, such as a-chloroacetic acid, B-chlorpropionic acid, 'y-chlorbutyric acid, etc., in the presence of an alkaline material, such as an alkali metal or alkaline earth metal hydroxide, to form the desired betaine.

The above compounds and radicals have been cited as illustrative of the materials which can be used in the presentinvention and it is to be pointed out that such is not to be construed as limitative of the invention, but that corresponding and equivalent compounds and radicals may be used within the spirit of the inventive concept.

The invention will be further illustrated in more specific detail by the following examples. It should be understood, however, that although these examples may describe in more particular detail some of the very specific features of the invention, they are given primarily for purposes of illustration and the invention in its broader aspects is not to be construed as limited thereto.

Preparation of intermediate am ides EXAMPLE 1. N,'N-BIS- OLEYLAMIDOPR OPYL) -N- METHYLA MI NE CnHai-tao ONHCHzCHzCHa CH /N CHEM-33C O NHCHzCHzCHs Reaetants Mole(s) Gms.

Acintol Fatty Acid 1 1. 0 294 Bis-(B-aminopropyl)-methylamine 0.525 76 0 1.0 mole) had collected in the water trap. A sample was titrated and found to contain less than 1% uncombined carboxylic acid. It was therefore stripped free of xylene and unreacted amine and used directly for the preparation of the betaine. Yield, 97%.

EXAMPLE 2.-N,1NBIS- OLEYLAMIDOPROPYL) -AMINE CHEM-33C ONHCIIZCHQOEZ }I /N C at-33C O NH C HzC HzCIIz Reactants Mole(s) Gms.

Actinol FA 1 l. 5 441. Bis-(3-aminopropyl)-amine 0. 788 103 By the procedure in Example 1, the mixture was heated for 11 hours at l45l95 C. Stripping gave a 98% yield of product.

EXAMPLE 3.-N, N-BIS- STE-ARAMIDOPROPYL) -N- METHYLAMI'NE Ci6-i7 ai-saCONHCH2CH2C z CH C ia-rlllai-aac ONHCHzC I-IzC Hg Reactants i Mole (s) Gms.

Hydroiol 405 1. 277 Bis-(3-aminopr0pyD-methylamine 0. 525 76 Hydrofol 405 is a commercial grade of stearic acid and contains about 65% stearic acid, 28% palmitic acid, 2% myristic acid and 6% oleic acid. After heating for six hours at 152189 C. and stripping, the product yield was 97%. It set to a hard yellow Wax.

EXAMPLE 4.- N,N BIS- STEARAMIDOPROPYL) AMI-NE Reactants l Mole(s) Gms.

Hydrofol 405 1. 3 360 Bis-(3-aminopropyh-amin 0. 683 89 Heating for ten hours at 183185 C. and stripping gave a 100% yield of the amide.

A similar preparation in which nitrogen gas was substituted for xylene gave a quantitative yield after sixteen hours at 138185 C.

EXAMPLE 5.N,N-BIS- STEARAMID OISOPROPYL AMINE Reactants Mole(s) Gms.

Hydrofol 405 A 1. 0 277 Dipropylene triamine 0.5 67

Employing both nitrogen and xylene, a 96% yield was obtained after twenty-two hours at 147184 C.

EXAMPLE *6 .-*N, NBIS- STEAR AMID O ETHYL) -AMI NE Reactants Molets) Gms.

Hydrofol 405 1. 0 277 Diethylenetriamine 0. 57

Similar to Example 5 but heated for six hours at 165- 173 C. Yield, 98%.

EXAMPLE 7.N-LAURA%%3ggROPYL-N,N-DIMETHYL- Reactants M0le(s) Gms.

Neoiat 11 310 3-dimethylaminopropylamine Similar to Example 5 but benzene substituted for xylene and only 25% of amine added at start. Rest added drop- 4 Wise over a seven hour period. Total heating time was twenty-eight hours at 113-1645 C. Yield, 98%. (Neofat 11 is a mixture of fatty acids obtained by fractional distillation processes and comprises lauric acid, 9% myristic acid and 1% oleic acid.)

Preparation of intermediate esters EXAMPLE S. N-STEAROYLOXYETHYL-N,N BIS (2-HYDROXYETHYL) -AMINE O 1] 01111 0 0 0 H2051 0 H20 1120 H C H2 0 112 O H Reactants M01e(s) Gms.

Hydrofol 405 1.0 277 Triethanolamine 1. 0 147 Similar to Example 5 but heated for four hours at 150- C. A light tan wax was obtained in a 90% yield.

EXAMPLE 9 .--N,N-BIS (STEAROYLOXYETHYL) -N- (2-HYDROXYETHYL) AMI=NE Reactants Mole(s) Gms.

Hydrofol 405 1. 0 277 Triethanolamine 0. 5

Heating for eleven hours at 141190 C. by previous methods gave a tan wax, 96% yield.

EXAMPLE 10.N,N-BIS-(STEAROYLOXYETHYL)-N-METH- YLAMINE Beactants M0le(s) Gms.

Hydroiol 405 D iethanolmethylamine.

Thirteen hours at 135-160 C. gave a 100% yield of the ester.

Preparation of intermediate tertiary amines The amide was dissolved in 300 g. of isopropyl alcohol and treated with the ethylene oxide for 1.6 hours at 78- 81.5 C. Stripping gave the hydroxyethylated product in quantitative yield.

EXAMPLE 12.-N,N-BIS-(STEARAMIDOPROPYD-HYDROXY- ETHYLAMINE Reaetants Equiva- Gms.

lents N,N-bis-(stearamidopropyl) amine (Ex. 4) 0.65 421 Ethylene oxide 29 Isopropyl alcohol 420 As Example 11 except the mixture was treated for two hours at 7382 C.

EXAMPLE 13.N,N BIS (STEARAMIDOISOPROPYL) HY- DROXYETHYLAMINE Reactants Equiva- Gms.

lents N,N-bis-(stearamidoispropyl)amine (Ex. 0.5 298 Ethylene oxide 21. 6 Isopropyl alcohol 237 Treated for 2.3 hours at 50-90 C. Quantitative yield of hydroxyethylated product.

E XAMPLE 1g.N,N-BI1S-(STEARAMIDOETHYL)-HYDROXY- THYLAMINE Reactants I Equiva- Gms.

lents N ,N-bis-(stearamidoethyl)-amine (Ex. 6) 0. 5 298 Ethylene oxide 23. 5 Isopropyl alcohol 237 Treated for 2.8 hours at 67-80 C. Quantitative yield.

Preparafion of betaines EXAMPLE 15. N,N-BIS(OLEYLAMIDROPROPYD-N-METH- YL-N-CARBOXYMETHYLAMMONIUM BETAINE The chloracetic acid was suspended in the water in a flask of suitable size equipped with a stirrer, thermometer, and reflux condenser. The acid was neutralized with the sodium hydroxide at a 40-50% aqueous solution while cooled in an ice bath. The amine in alcohol was added and-the mixture refluxed for five hours.-

At the end 'of' the reaction the mixture was diluted with alcohol and evaporated to dryness." The resulting solid was dissolved in benzene and the insoluble salt (sodium chloride) removed by filtration'The filtrate was evaporated to dryness to give a brown paste in quantitative yield. v

The product'was useful as a 'germicide and killed -24- hour' cultures of Salmonella typhosa in 10 minutes at C. in dilutions up to 1:1000;

It was also useful as a softening agent for textiles, particularly cottons. i

It is to be noted that the F -M-R grouping inExample 15 is, in effect, an alkenylamidoalkyl radical, as compared to an alkylaminoalkyl radical (Example 17), an alkyloyloxyalkyl radical (Example 21), an alkylcarbamylalkyl radical (Example 23), an alkarylamidoalkyl radical (Example 31), a cycloalkylarnidoalkyl radical (Example 33) or the thio-substituted alkylcarbamylaminoalkyl, alkylamidoalkyl and arylamidoalkyl radicals (Examples 34, 35, 36).

EXAMPLE 16.N,N BIS (0 LE YLAMTDOPROPYL) N,N BIS (CfilgggIYMETHYLAMI/IONIUM) BETAINE, MONOSODI- 017 330 ONHOHrCHzCEz CHzCO O- Reactants Equlva Gms.

lents N,N-bis-(oleylamidopropyD-amine (Ex. 2) 0. 26 176 Ohloracetic acid 0. 50 Sodium hydroxide. 0. 75 Ethanol (m1.) 35 Water (mL)- 75 Reflux for six hours and workup gave a quantitative yield of viscous brown liquid.

EXAMPLE 17.-N,N- BIS (STEARAMIDOPROPYL) N METH YL-CA RB OX YMETH YLAMMONIUM BETAINE CHHMCONHOHQCHQOHI CH3 CnHasCONHCHaCHzC z CHzCOO- Reaetants Gms.

Equivalents A reflux time of five hours and usual work 'up gave a yellow Wax (quantitative).

The product was useful as a cotton softener. It was also useful as a germicide and killed 24-hour cultures of Salmonella typhosa in' 10 minutes at 20 C. in dilutions up to 1:1000.

EXAMPLE l8.-N-(STEARAMIDOPR'OPYL)-N,N-DIMETHYL- N-CARBOXYMETHYLAMMONIUM BETAINE Five hours refluxing and workup gave jai quantitative yield of a white wax. The product was useful as a detergent and as an anti-staticagent.

EXAMPLE 19.-N,N BIS (OLEYLAMIDOPROPYL)-N-(2- IggflggffiYETHYL) -N-CARBOXY METHYL AMMONIUM onnuoonrtomomom' CHECHiOH E quivalents Reactants N,N-bis-(oleylamidopropyl)-N-(ZhydroxyhyD-amine (Ex. 11)

Chloracetic acid Sodium hydroxide... Isopropyl alcohol (ml.)+ Water (mL) 1 Including isopropyl alcohol.

EXAMPLE 20.N,N BIS (STEARAMIDOPROPYL)-N-(2- HYDROXYETHYL)- N CARBOXYMETHYL AMMONIUM BETAINE Isopropyl alcohol (ml.)+ Water (rnL) 1 Including isopropyl alcohol.

A quantitative yield of tan or brown wax was obtained after about six hours of reflux and recovery.

EXAMPLE 21.N STEAROYLOXYETHYLN,N-BIS-(3-HY- DROXYETHYL)-N-CARBOXYMETHYL AMMONIUM BE- TAINE 01111 0 O CHZCHZ CHaCHzOH 01120111011 CH2COO Reactants Equlva- Gms.

lents N-stearoyloxyethyl-N ,N-bis-(Q-hydroxyethyD-amine (Ex. 8) 200 Chloracetic acid Water mi The refluxing time was six and three-quarter hours. Quantitative yield of ten wax. The product was useful as a detergent and anti-static agent.

EXAMPLE 22.-N,N BIS (STEAROYLOXYETHYL)-N-(2- HYDROXYETHYL) N CARBOXYMETHYL AMMONIUM BETAINE OITHMCOOCHZCQI 01110112011 C7H35COOCH2CHZ CHZCOO' Reaetants E quiva- Gms.

lents N ,N-bis- (stearoyloxyethyl) -N-(2-hydroxyethyD-amine (Ex. 9) 0. 086 200 Chloroacetic acid..- 0. 086 Sodium hydroxide 0. 086 Ethanol (m.l.).... 150 W ater (1111.)

Six and three-quarter hours reflux gave a 92% yield of tan wax. EXAMPLE 23.N,N BIS (N OCTADECYLCARBAMYL- ETHYL) V- (2 HYDROXYETHYL) N-CARBOXYMETHYL AMMONIUM BETAINE of a quantitative yield of a brown wax. It possessed utility as a textile softener.

EXAMPLE 24.-N,-N BIS (S-TEARAMIDOISOPROPYL) -1N- (2-HYDROXYETHYL) N CARBOXYMETHYL AMMO- NIUM BETAINE onuaiooNrlorrrog CHnCHzOH C H; N G11H CONHCHQCIDH CHZCO O- Reaotants Equlva- Gms.

lents 0. 50 l 560 0. 50 Sodium hydroxide 0. 50 Isopropyl alcohol (ml.)+. Water (ml.)+ 75 1 Including lsopropyl alcohol.

Seven hours refluxing gave an orange-brown paste. Recovery was quantitative.

EXAMPLE 25.-N.N BIS (STEARAMIDOETHYL) -N-(2- I-IYDROXYETHYL) N CARBOXYMET'HYL AMMONIUM BETAINE C17H C O NHCII2C Hi CH OHZO H 01 E 0 ONHCHzC H: 0 H10 0 O- Reaetants Equlva- Gms.

lents N,N-bis-(stearamldoethyl)-N-(2-hydroxyethyD-amlne 0. 493 l 555 Chloroacetic acid. 0. 493

Sodium hydroxide Isopropyl alcohol (ml Water (ml)- l Inoludlng isopropyl alcohol.

A reflux time of five hours and workup gave a quantita= tive yield of a tan wax.

EXAMPLE 26.--N;N BIS (STEAROYLOXYETHYm-N- METHYL-N-CARBOXYMETHYLAMMONIUM BETAI-NE 01111 0 0 O CHaCHa CH:

01711350 0 0 CHaC H2 CHQC O O Reactants Equiva- Gms.

lents N,N-bls- (stearoyloxyethyl) -N-methylamlne 0. O9 307 Chloroacetic acid 0. 09

Sodium hydroxide-.. 0. 09

Isopropyl alcohol (m1.) 300 Water (m1.) 50

Seven and one-quarter hours was suificient reflux time to give a 94% recovery of a tan wax product. It was useful as a cotton softener.

EXAMPLE 27.N (LAURAMIDOPROPY'L) bLN-DIMETE YL-N-CARBOXYMETHYLAMMONIUM BETAINE C11Hr CONHCH2CH2CH2 CH3 CH: OHzC O 0- Reactants Equiva- Gms.

lents N-(lauramidopropyD-N N-dimethylamine. 1. 57 426 Ghloroacetic acid 1. 7

Sodium hydroxid 1.

Ethanol (ml) Water (ml).

Heated at reflux for nine and one-half hours; gave quantitative yield of soft tan wax.

EXAMPLE 28.P OLYETIHYLENE GLYOOL PRODUCT 011E350 ONHCHaCHaC\Hz /CHICH20(OH2CH20 fl-8H Actually reacted. Excess used. 7

The betaine was dissolved in the alcohol, the mixture heated to 20 C. and ethylene oxide added at 6278 C. for 2% hours. The final product, a polyethenoxy derivative obtained in quantitative yield, was a brown 47% solution.

This material contained 2.6 mols of combined ethylene oxide for each mol of the original betaine. It was therefore a mixture of two or more ethylene oxide condensation products.

EXAMPLE 29.POLYETHYLENE GLYCOL PRODUCT OnH sOoNHcHrCHrOgz /CH2CHzO (CH2CH2O)80H cnHascoNHCHzCHtcfit CHzCOO Reactants Equiva- Gms.

lents Rename in Ex. 19 0. 1 88 Ethylene oxide *3. Isopropyl alcohol 111 Reactants Mole(s) Gms.

Propionic Acid 1 74 Bis-(3-aminopropyl) -methylamine 0. 525 76 The procedures set forth in Example 1 were followed substantially as set forth therein. The yield was quantitative.

N,N-BIS(PROPYLAMIDOPROPYL)-N-METHYL-N- CARBOXYMETHYL AMMONIUM BETAI'NE CaH CONHCH2CH2CHz CHaCOO The procedures of Example were followed, using substantially equal molal amounts of amine, chloracetic acid and sodium hydroxide. The yield was quantitative.

EXAMPLE '3'1.N,-N-BIS(DODECYLBENZYLAMIDO- PR-OPYL) =N-DECYLAMI NE CmHzaCalLC ONHCHzCHzCE: C10H2l CuHnCalLC ONHCHzCHzCfi:

Reactants Mole (s) Gms.

p-Dodecyl benzolc acid 1 293 Bis-(3-aminopropyl) -decylam.ine 0. 525 184 10, Procedures as in Example 1.

N ,N-BIS DODECYLBENZYLAMIDOPROPYL) N -DECYL-4N CARBOXYETHYL AMMONIUM BETATNE C12Ha5CaH4CONHCHzCH2CHa CHrCH2COO- 7 Using chlorpropionic acid .and sodium hydroxide, as Example 15.

EXAMPLE '32.N,'N-BIS( CYCLOHEXYLAMIDOPR'OPYL) N-OCTYL-N CARBOXYMETHYL AMMOINIUM BETAIINE CaHuC ONHOHzCHzCH': Y CsHn csHuCoNHCHaCHnClz CHQCOO- Using cyclohexyl carboxylic acid and bis-(3- aminopropyl) -octylamin'e to form the intermediate tertiary amine and chloracetic acid and sodium hydroxide to form the betaine.

Using N-dodecylurea and; 3-aminopropyldimethylamine in the formation of the tertiary amine, followed by its reaction with chloracetic acid and sodium hydroxide in the formation of the betaine.

' EXAMPLE 34 r CHHZENHCSNHCHQCHRCHZZP'LCHZCOO- Using N-dodecyl thio-urea and 3-aminopropyldimethylamine in the formation of the tertiary amine, followed by its reaction with chloracetic acid and sodium hydroxide in the formation of the betaine. I

EXAMPLE 35 (3H3 oimooNmomm cmooov g g CH3 I v Using butyric acid and-dimethylaminolaurylamine to form thetertia-ry amine and chloracetic acid and sodium hydroxide to form the betaine.

EXAMPLE 36 Using ethanethionic acid and a slight excess of 3- dimethylaminopropylamine in the formation of the intermediate tertiary amine and chloropropionic acid and sodium hydroxide in the formation of the betaine.

EXAMPLE 37 Using thiobenzoic acid and a slight excess of S-diethylaminopropyl amine in the formation of the intermediate tertiary amine and chlorobutyric acid in the formation of the betaine.

hours at 37 C. The following table indicates the results obtained.

TABLE 1 Evidence of Growth Alter- Mins. Mins. Mins.

Concentration of Betalne;

Legend: indicates growth, indicates no growth.

As a control and comparison, a similar test procedure was used on a 35% solids solution of stearamidopropyldimethyl-B-hydroxyammonium dihydrogen phosphate (SP). This product (SP) is not a product of the present invention but was selected as it bears some structural resemblance to the products of the present invention. The following table indicates the results obtained.

TABLE 2 Evidence of Growth Atten- 5 Mins. 10 Mins. 15 Mins.

Concentration of SP:

Legend: indicates growth, indicates no growth.

The above tables indicate that a 1:1500 dilution of the betaine killed a 24-hour culture of Salmonella typhosa in 10 minutes at a temperature of C. This corresponds to a 1:85 dilution of phenol. The phenol co- 12 efficient is therefore 18.1. With regard to product SP, the 24-hour culture of Salmonella typhosa was killed in 10 minutes at 20 C. with a dilution of 1:25. This corresponds to a 1:85 dilution of phenol. The phenol coefiicient is therefore 0.3.

Although we have described specific examples of our inventive concept, we consider the broad aspects of the same not to be limited to the specific substances mentioned therein but to include various other compounds of equivalent function and constitution as set forth in the claims appended hereto. It is understood that any suitable changes, modifications and variations may be made without departing from the spirit and scope of the invention.

We claim: 1. Betaines having the formula Rs R1( iNH-Rl1 1 mc 0 0 where R is aryl, R and R are alkylene radicals of from 1 to 12 carbon atoms, R is a member of the group consisting of -C I-I in which n is a whole number from 1 to 10 and -C H .OH in which n is a whole number from 1 to 10 and (C H .O) H in which x is a whole number from 2 to about and R is a member of the group consisting of R R1 C NH RT -R -COOH and -R COOMe in which R R R and R are as defined above and Me is a monovalent saltforming radical, and X is selected from the group consisting of O and S.

LORRAINE A. WEIN-BERGER, Primary Examiner. A. SUTTO, M. WEBSTER, Assistant Examiners.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent NO. 3,366,671 January 30, 1968 Frank M. Cowen et al.

It is certified that error appears in the above identified patent and that said Letters Patent are hereby corrected as shown below:-

Column 1 line 29 "B-", second occurrence should read D-- Column 7 third table third column, line 6 thereof, after "Water (ml.) insert- 40 line 57 "(N-OCTADECYLCARBAMYL" should read (N-OCTADECYLCARBAMYL same column 7 ourth table first column, line 1 thereof, "N,N-bis (N-stearylpropionamide)-" should read N,N-Bis-(Noctadecyclcarbamylethyl) Column 9 line 43 )CH" should read Signed and sealed this 7th day of October 1969.

(SEAL) Attest:

Edward M. Fletcher, Jr.

Attesting Officer Commissioner of Patents WILLIAM E. SCHUYLER, JR. 

1. BETAINES HAVING THE FORMULA 